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两种马来布鲁线虫丝虫疫苗候选抗原(BmALT-2和BmVAH)的组合可增强沙鼠的免疫反应和保护作用。

A combination of two Brugia malayi filarial vaccine candidate antigens (BmALT-2 and BmVAH) enhances immune responses and protection in jirds.

作者信息

Anand S B, Kodumudi K N, Reddy M V, Kaliraj P

机构信息

Department of Genetic Engineering, School of Biotechnology, Madurai Kamaraj University, Madurai - 625021, India.

出版信息

J Helminthol. 2011 Dec;85(4):442-52. doi: 10.1017/S0022149X10000799. Epub 2011 Jan 4.

Abstract

In this study filarial recombinant protein or DNA vaccine constructs encoding BmALT-2 and BmVAH as single or as cocktail antigens were evaluated. Male jirds were immunized intramuscularly with DNA vaccine constructs or were immunized intraperitoneally with protein vaccine. The single and bicistronic DNA constructs induced substantial interferon-γ responses in spleen cells; antigen-specific responses were higher following immunization with the bicistronic cocktail construct and evoked a significant protective response of 57% in jirds challenged with Brugia malayi that was similar in the antibody-dependent cellular cytotoxicity (ADCC) assay and micropore chamber experiment. The cocktail protein vaccines induced a mixture of IgG2a (Th1) and IgG1 (Th2) responses with 80% protective response when challenged with B. malayi infective larvae. However, the single protein vaccine rALT-2 induced Th2 (IgG1/IgG3) with a 70% protective response and rVAH induced Th1 (IgG2a) with a lower proliferative response with 60% protection following challenge with B. malayi infective larvae. These results suggest that filarial cocktail protein vaccines are able to elicit substantial immune and protective responses when compared with single antigen vaccination in suitably vaccinated jirds.

摘要

在本研究中,对编码BmALT-2和BmVAH作为单一或混合抗原的丝虫重组蛋白或DNA疫苗构建体进行了评估。雄性沙鼠通过肌肉注射DNA疫苗构建体进行免疫,或通过腹腔注射蛋白质疫苗进行免疫。单一和双顺反子DNA构建体在脾细胞中诱导了大量的干扰素-γ反应;用双顺反子混合构建体免疫后,抗原特异性反应更高,并在用马来布鲁线虫攻击的沙鼠中引发了57%的显著保护反应,这在抗体依赖性细胞毒性(ADCC)试验和微孔室实验中相似。混合蛋白质疫苗在用马来布鲁线虫感染性幼虫攻击时诱导了IgG2a(Th1)和IgG1(Th2)反应的混合,保护反应率为80%。然而,单一蛋白质疫苗rALT-2诱导Th2(IgG1/IgG3),保护反应率为70%,rVAH诱导Th1(IgG2a),在用马来布鲁线虫感染性幼虫攻击后增殖反应较低,保护率为60%。这些结果表明,与在适当免疫的沙鼠中进行单一抗原疫苗接种相比,丝虫混合蛋白质疫苗能够引发大量的免疫和保护反应。

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